Regulation of Extrahepatic Apolipoprotein Serum Amyloid A (ApoSAA) Gene Expression by Interleukin‐1α Alone: Synthesis and Secretion of ApoSAA by Cultured Aortic Smooth Muscle Cells
Regulation of Extrahepatic Apolipoprotein Serum Amyloid A (ApoSAA) Gene Expression by Interleukin‐1α Alone: Synthesis and Secretion of ApoSAA by Cultured Aortic Smooth Muscle Cells
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单独通过白细胞介素-1α 调节肝外载脂蛋白血清淀粉样蛋白 A (ApoSAA) 基因表达：培养的主动脉平滑肌细胞合成和分泌 ApoSAA
DOI：
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发表时间：
1997
影响因子：
3.7
通讯作者：
B. Schreiber
中科院分区：
文献类型：
--
作者：
Y. Kumon;J. Sipe;C. Brinckerhoff;B. Schreiber
血清淀粉样蛋白A载脂蛋白（apoSAA）似乎会损害高密度脂蛋白预防动脉粥样硬化的能力，在已知刺激肝脏急性期apoSAA （A‐apoSAA）合成的细胞因子存在的情况下，确定主动脉平滑肌细胞是否有助于局部apoSAA池是有意义的。在这项研究中，我们在培养的新生兔主动脉平滑肌细胞中监测了A‐apoSAA合成的调节。组成型apoSAA3基因表达极少，只有通过逆转录聚合酶链反应扩增mRNA才能检测到。IL‐1α刺激ApoSAA3基因表达和蛋白合成；低至0.01ng/ml的IL - 1α刺激apoSAA3 mRNA稳态水平的增加。有趣的是，IL - 6（除IL - 1α外，人类肝癌细胞合成A‐apoSAA也需要IL - 6）对平滑肌细胞合成apoSAA3几乎没有影响。在时间过程中，我们发现在添加细胞因子后1-2h， apoSAA3 mRNA水平的刺激是明显的，并且在细胞因子存在的情况下，apoSAA3 mRNA水平保持升高至少48小时。使用针对apoSAA3的抗血清进行免疫沉淀发现，IL‐1α刺激apoSAA3蛋白的合成和分泌，其方式与apoSAA3 mRNA的表达一致。讨论了这些发现在动脉粥样硬化发生中的意义。
Serum amyloid A apolipoproteins (apoSAA) appear to compromise the ability of high density lipoprotein to protect against atherosclerosis and it is of interest to determine whether aortic smooth muscle cells can contribute to local pools of apoSAA in the presence of cytokines that are known to stimulate acute phase apoSAA (A‐apoSAA) synthesis in the liver. In this study, the regulation of A‐apoSAA synthesis was monitored in cultured neonatal rabbit aortic smooth muscle cells. Constitutive apoSAA3 gene expression was minimal, and only detectable by amplification of the mRNA by reverse transcriptase–polymerase chain reaction. ApoSAA3 gene expression and protein synthesis were stimulated by IL‐1α; as little as 0.01ng/ml of IL‐1α stimulated an increase in steady state levels of apoSAA3 mRNA. Interestingly, IL‐6 (which is required in addition to IL‐1α for the optimal synthesis of A‐apoSAA by human hepatoma cells) had little if any effect on apoSAA3 synthesis by the smooth muscle cells. In a time course, it was shown that the stimulation of apoSAA3 mRNA levels was apparent by 1–2h after the addition of cytokine, and that levels remained elevated in the presence of the cytokine for at least 48h. Immunoprecipitation using an antiserum directed against apoSAA3 revealed that IL‐1α stimulated the synthesis and secretion of apoSAA3 protein in a manner that was consistent with apoSAA3 mRNA expression. The implications of these findings in atherogenesis are discussed.
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影响因子：
15.9
作者：
GALIS, ZS;SUKHOVA, GK;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
20.1
作者：
GALIS, ZS;MUSZYNSKI, M;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
33.6
作者：
G. Owens
通讯作者：
G. Owens
β-VLDL 诱导单核吞噬细胞产生的生长增强活性的改变。
影响因子：
5.3
作者：
Schreiber,BM;Martin,BM;Hollander,W;Franzblau,C
通讯作者：
Franzblau,C
长期用 β VLDL 治疗新生儿主动脉平滑肌细胞会诱导胆固醇积累。
影响因子：
5.3
作者：
Schreiber,BM;Jones,HV;Toselli,P;Franzblau,C
通讯作者：
Franzblau,C